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Association of baseline characteristics with adverse events (AEs) in the PROpel trial of olaparib (ola) plus abiraterone (abi) as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC).

2024· article· en· W4400412464 on OpenAlexaff
Andrew J. Armstrong, Fred Saad, Mototsugu Oya, Neal D. Shore, Giuseppe Procopio, Karina Vianna, Niven Mehra, Mustafa Özgüroğlu, Craig Gedye, Emma Brown, Friederike Schlürmann, Ji Youl Lee, Jae Young Joung, Mikio Sugimoto, Urban Emmenegger, Emma Oscroft, Bob Shaw, Maria G. Winter, Christian Hosius, Noel W. Clarke

Bibliographic record

VenueJournal of Clinical Oncology · 2024
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsSunnybrook HospitalCentre Hospitalier de l’Université de Montréal
Fundersnot available
KeywordsMedicineProstate cancerOlaparibAbirateroneInternal medicineAdverse effectOncologyAbiraterone acetateCancerAndrogen deprivation therapyAndrogen receptor

Abstract

fetched live from OpenAlex

e17030 Background: The PROpel trial (NCT03732820) met its primary endpoint and showed a statistically significant radiographic progression-free survival benefit (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.0001) with ola + abi vs placebo + abi in 1L mCRPC; whilst not statistically significant, overall survival (OS) was numerically prolonged (median 42.1 vs 34.7 months; HR 0.81, 95% CI 0.67–1.00; P=0.0544). To further inform clinical decision making, we provide exploratory post hoc analysis investigating the relationship between selected patient baseline characteristics and AEs for ola + abi. Methods: Anemia and venous thromboembolism events (VTEs) were identified as the only grade (Gr) ≥3 AEs or AEs of special interest reported in >20 (>5.0%) patients (pts) in the ola + abi arm (data cutoff 12 Oct 2022). Baseline characteristics were correlated with AEs using Cox regression by backwards elimination and analysis with AEs as dependent variables. Baseline characteristics assessed included: age (<70 or ≥70 y), time since diagnosis ( 20), Gleason score (<9 or 9–10), homologous recombination repair mutation status (HRRm, non-HRRm or unknown), race (white or non-white), prior docetaxel at metastatic hormone-sensitive prostate cancer (yes or no), pain (symptomatic or asymptomatic/mildly symptomatic), type of progression (prostate-specific antigen [PSA], radiographic or both), prior radiotherapy (yes or no) and albumin, creatinine, lactate dehydrogenase, alkaline phosphatase (ALP), hemoglobin (10<12 or ≥12) and log PSA levels. Results: 398 pts received ola + abi. 64 (16.1%) had Gr ≥3 anemia and 34 (8.5%) a VTE. Baseline characteristics correlated significantly with increased risk of these AEs as shown (Table); characteristics not shown were not associated with AEs. Conclusions: These results provide insight into which baseline characteristics correlate with the risk of Gr ≥3 anemia. Pts with abnormal ALP, pre-existing anemia, ECOG PS 1 or age ≥70 years could be at higher risk and the development of Gr ≥3 anemia during treatment with ola + abi should be monitored. Clinical trial information: NCT03732820 . [Table: see text]

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.156
GPT teacher head0.490
Teacher spread0.333 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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